Abstract
Metabolic reprogramming is a hallmark of cancer and has proven to be critical in viral infections. Metabolic reprogramming provides the cell with energy and biomass for large-scale biosynthesis. Based on studies of the cellular changes that contribute to metabolic reprogramming, seven main hallmarks can be identified: (1) increased glycolysis and lactic acid, (2) increased glutaminolysis, (3) increased pentose phosphate pathway, (4) mitochondrial changes, (5) increased lipid metabolism, (6) changes in amino acid metabolism, and (7) changes in other biosynthetic and bioenergetic pathways. Viruses depend on metabolic reprogramming to increase biomass to fuel viral genome replication and production of new virions. Viruses take advantage of the non-metabolic effects of metabolic reprogramming, creating an anti-apoptotic environment and evading the immune system. Other non-metabolic effects can negatively affect cellular function. Understanding the role metabolic reprogramming plays in viral pathogenesis may provide better therapeutic targets for antivirals.
Highlights
Metabolic reprogramming is a crucial area of study in cancer and is listed as a hallmark of cancer [1]
We classified changes in cellular metabolism that contribute to metabolic reprogramming in six main hallmarks: (1) increased glycolysis and lactic acid, (2) increased pentose phosphate pathway (PPP), (3) increased glutaminolysis, (4) mitochondrial changes, (5) increased lipid metabolism, (6) changes in amino acid metabolism, and (7) changes in other biosynthetic and bioenergetic pathways (Figure 1)
These results indicate that human cytomegalovirus (HCMV) increases the glutaminolysis to supplement the TCA cycle and maintain the TCA cycle intermediates along with adenosine triphosphate (ATP) production in the mitochondria [144]
Summary
Metabolic reprogramming is a crucial area of study in cancer and is listed as a hallmark of cancer [1]. Dr Otto Warburg first described metabolic reprogramming while studying the properties of tumorigenic cells He observed an increase in the metabolism of glucose, known as glycolysis, and a subsequent high concentration of lactic acid [2]. The finding that cancer cells act as hypoxic cells was surprising The term for this phenomenon is the Warburg effect and is defined as an increase in glucose uptake and increase in lactate production even in the presence of oxygen [3]. A significant role of the Warburg effect is to provide the rapidly proliferating cancer cells with enough “building blocks” to fuel cellular division These building blocks are known as biomass (nucleotides, amino acids, and lipids) and are essential for creating new cells [4]. We summarized the current literature that defines the hallmarks of metabolic reprogramming and their involvement in viral replication
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